We will test the hypothesis that alcohol physical dependence is caused by changes in the physical properties of biomembranes. We will follow up our findings that ethanol-tolerant mice have ethanol-tolerant membranes and will examine the sensitivity of membranes to ethanol in different genetic populations of mice. The membranes will be examined by electron paramagnetic resonance as a means of estimating their general fluidity. We will also examine the chemical composition of mouse membranes, especially with respect to cholesterol and phospholipids. Mice will be treated chronically with ethanol by means of liquid diets or inhalation. The hypothesis to be tested is that cell membranes adapt to the chronic presence of ethanol. We will see whether the membranes become resistant to ethanol or whether ethanol fails to dissolve in such membranes. Rapidly developing tolerance to ethanol will be further explored, to see whether changes in membrane lipids accompany this phenomenon and whether it may explain some apparently innate differences between animals in their sensitivity to ethanol.